IMMUNE EVASION BY HUMAN PAPILLOMAVIRUS

人乳头瘤病毒的免疫逃避

• 批准号: 6487286
• 负责人: Dennis J. McCance
• 金额: $ 15万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6487286
• 关键词: CD40 molecule; Langerhans' cell; MHC class I antigen; T lymphocyte; cell differentiation; chemotaxis; clinical research; cytokine; dendritic cells; human papillomavirus; human subject; keratinocyte; microorganism immunology; protein biosynthesis; transfection; virus infection mechanism; virus protein

Human papillomaviruses (HPV) infect and replicate in stratified epithelial cells of the skin and mucosal surfaces where they can cause benign lesions, or pre-malignant and malignant disease. The papillomaviruses can therefore by divided into low and high risk types depending on their pathology. A common feature of both groups is their ability to persist in the host without stimulating any effective immune response, so that lesions persist for months or even years. Regression does, however, occur spontaneously and is immunogically mediated.. The natural history of infection suggests that the virus has evolved mechanisms to impair an effective immune response from being generated by the host. The host cell of the virus is the keratinocyte, have evidence that the E6 proteins of HPV type 16 inhibits the production of cytokines produced by keratinocytes and so may inhibit stimulation of an effective immune response. In this project we wish to expand these initial observations to determine if other HPV types modulate stimulatory or inhibitory cytokines and to investigate if keratinocytes expressing HPV genes change the functional properties of skin dendritic cells, so that they can no longer stimulate an effective immune response.

人乳头瘤病毒(HPV)在皮肤和粘膜表面的层状上皮细胞中感染和复制，在那里它们可以引起良性病变，或癌前和恶性疾病。因此，根据其病理情况，乳头瘤病毒可分为低危型和高危型。这两组人的一个共同特征是，他们能够在不刺激任何有效免疫反应的情况下在宿主中持续存在，因此病变持续数月甚至数年。然而，退化确实是自发发生的，并且是由免疫调节的。感染的自然历史表明，该病毒已经进化出机制，以削弱宿主产生的有效免疫反应。病毒的宿主细胞是角质形成细胞，有证据表明HPV16型E6蛋白抑制角质形成细胞产生细胞因子，因此可能抑制有效免疫反应的刺激。在这个项目中，我们希望扩大这些初步观察，以确定其他类型的HPV是否调节刺激性或抑制性细胞因子，并调查表达HPV基因的角质形成细胞是否改变了皮肤树突状细胞的功能特性，使其不再能够刺激有效的免疫反应。